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Background: Gemcitabine together with nab-paclitaxel (GnP) has been shown to improve outcomes in patients with pancreatic ductal adenocarcinoma (PDAC). However, the predictive markers for treatment effects remain unclear. This study aimed to identify early prognostic factors in patients with PDAC receiving GnP. Patients and Methods: We analyzed 113 patients who received GnP for PDAC and evaluated the relationship between clinical factors and outcomes. Results: The median survival time (MST) was 1.2 years. In multivariate analysis, baseline carbohydrate antigen 19-9 (CA19-9) ≥747 U/ml [hazard ratio (HR)=1.9], baseline controlling nutrition status (CONUT) score ≥5 (HR=3.7) and changing rate of CA19-9 after two GnP cycles ≥0.69 (HR=3.7) were independent risk factors for poor prognosis. When examining outcomes according to pre-chemotherapeutic measurable factors (baseline CA19-9 and CONUT), the MSTs of patients with pre-chemotherapeutic zero risk factors (pre-low-risk group, n=63) and one or more risk factors (pre-high-risk group, n=50) were 1.7 and 0.65 years (p

The controlling nutritional status (CONUT) score is a useful biomarker to evaluate undernutrition. However, there have been few reports describing the correlation between postoperative complications and the CONUT score for pancreatic cancer. Therefore, this study aimed to assess the impact of the CONUT score on the postoperative complications of pancreaticoduodenectomy (PD) in patients with pancreatic cancer. We retrospectively analyzed 206 consecutive patients with pancreatic cancer who underwent PD over a 12-year duration at our institution. The patients were divided into two groups based on preoperative CONUT scores; their clinicopathological characteristics and surgical outcomes were compared. Furthermore, we compared the CONUT score with preoperative clinical factors and several nutritional biomarkers for postoperative complications using univariate and multivariate analyses. Postoperative complications of Clavien–Dindo grade ≥ IIIa and those of Clavien–Dindo grade ≥ IIIb occurred in 29 (14.1%) and 9 (4.4%) patients, respectively. The high CONUT score (≥5) group indicated that patients with an undernutrition status had a higher postoperative complication rate, poorer relapse-free survival, and overall survival rates than the low CONUT score (≤4) group. Among preoperative clinical factors, a high CONUT score was an independent risk factor for severe postoperative complications. The CONUT score may be a useful parameter in the identification of patients undergoing pancreatic surgery who are susceptible to postoperative complications.

To evaluate the surgical outcomes of patients with gallbladder cancer (GBC) with jaundice due to as-yet unelucidated prognostic factors. A total of 348 GBC patients underwent resection at our institute between 1985 and 2016. Of these, 67 had jaundice (serum total bilirubin ≥ 2 mg/dL). Preoperative biliary drainage was performed, with portal vein embolization as required. All patients underwent radical surgery. We retrospectively evaluated the outcomes, performed multivariate analysis for overall survival, and compared our findings to those reported in the literature. The 5-year survival rate of M0 (no distant metastasis) GBC patients with jaundice, who underwent resectional surgery, was 21.9%, versus 68.3% in those without jaundice (p < 0.05). Since 2000, surgical mortality in GBC patients with jaundice has decreased from 12 to 6.8%. Patients with jaundice had more advanced disease and underwent major hepatectomies and vascular resections; however, preoperative jaundice alone was not a prognostic factor. Multivariate analysis of jaundiced patients revealed that percutaneous biliary drainage (PTBD) (vis-a-vis endoscopic drainage [EBD], hazard ratio [HR] 2.82), postoperative morbidity (Clavien–Dindo classification ≥ 3, HR 2.31), and distant metastasis (HR 1.85) were predictors of poor long-term survival. The 5-year survival and peritoneal recurrence rates in M0 patients with jaundice were 16% and 44%, respectively, for patients with PTBD and 39% (p < 0.05) and 13% (p = 0.07) for those with EBD. M0 GBC patients with jaundice should undergo surgery if R0 resection is possible. Preoperative EBD may be superior to PTBD in M0 GBC patients with jaundice, although further studies are needed.

Objective Postoperative pancreatic fistula (POPF) is one of the severe complications that develop after pancreaticoduodenectomy (PD). This study aimed to assess the utility of preoperative clinicophysiologic findings as risk factors for POPF after PD. Summary of Background Data We enrolled 350 patients who underwent PD between 2007 and 2012 at Tokyo Women's Medical University. Methods In total, 350 patients who underwent PD between 2007 and 2012 were examined retrospectively. All patients were classified into 2 groups as follows: group A (no fistula/biochemical leak group, 289 patients) and group B (grade B/C of POPF group 61 patients). Variables, including operative characteristics, length of stay in hospital, morbidity, mortality, and data regarding preoperative clinicophysiologic parameters, were collected and analyzed as predictors of POPF for univariate and multivariate analyses. Results There were 213 male and 137 female patients. The mean age was 65.4 years (range, 21–87 years). Univariate analysis showed that sex (P = 0.047), amylase level (P = 0.032), prognostic nutritional index (PNI; P = 0.001), and C-reactive protein/albumin ratio (P = 0.005) were independent risk factors for POPF. In contrast, multivariate analysis showed that sex (P = 0.045) and PNI (P = 0.012) were independent risk factors for POPF. Conclusions Our results show that PNI (≤48.64 U/mL) and male sex were risk factors for POPF after PD, and especially, PNI can be suggested as an effective biomarker for POPF.

To evaluate the incidence, risk factors, management options, and outcomes of portal vein thrombosis following major hepatectomy for perihilar cholangiocarcinoma.A total of 177 perihilar cholangiocarcinoma patients who (1) underwent major hepatectomy and (2) underwent investigating the portal vein morphology, which was measured by rotating the reconstructed three-dimensional images after facilitating bone removal using Aquarius iNtuition workstation between 2002 and 2018, were included. Risk factors were evaluated using the Kaplan-Meier method and Cox proportional hazard models.Six patients developed portal vein thrombosis (3.4%) within a median time of 6.5 (range 0-22) days. Portal vein and hepatic artery resection were performed in 30% and 6% patients, respectively. A significant difference in the probability of the occurrence of portal vein thrombosis (PV) within 30 days was found among patients with portal vein resection, a postoperative portal vein angle100°, remnant portal vein diameter5.77 mm, main portal vein diameter13.4 mm, and blood loss (log-rank test, p = 0.003, p = 0.06, p0.0001, p = 0.01, and p = 0.03, respectively). Decreasing the portal vein angle and narrowing of the remnant PV diameter remained significant predictors on multivariate analysis (p = 0.027 and 0.002, respectively). Reoperation with thrombectomy was performed in four patients, and the other two patients were successfully treated with anticoagulants. All six patients subsequently recovered and were discharged between 25 and 70 days postoperatively.Narrowing of the remnant portal vein diameter and a decreased portal vein angle after major hepatectomy for perihilar cholangiocarcinoma are significant independent risk factors for postoperative portal vein thrombosis.

Background Upfront surgery is the standard treatment for resectable invasive intraductal papillary mucinous carcinoma; however, recurrence is common. Therefore, we investigated the recurrence, surgical outcome, and preoperative prognostic factors for recurrence in patients with resectable invasive intraductal papillary mucinous carcinoma. Methods We analyzed 111 patients who underwent upfront surgery for resectable invasive intraductal papillary mucinous carcinoma between 2000 and 2017 and evaluated the relationship among clinicopathologic factors, recurrence, and outcomes. Results The 5-year recurrence-free survival and disease-specific survival rates were 61% and 74%, respectively. The median time to recurrence was 1.1 years. In multivariate analysis, carbohydrate antigen 19-9 ≥83 U/mL (hazard ratio: 2.8 and 3.1), tumor size ≥2.2 cm (hazard ratio: 3.5 and 4.7), and pathologic tubular adenocarcinoma grade 2 (hazard ratio: 3.1 and 5.2) were risk factors for a shorter recurrence-free survival and disease-specific survival, respectively. Lymph node metastasis (hazard ratio: 3.9) was also a risk factor for a shorter disease-specific survival. When examining outcomes according to preoperatively measurable factors (carbohydrate antigen 19-9 ≥83 U/mL and tumor size ≥2.2 cm), the 5-year recurrence rates in patients with none (n = 47), 1 (n = 46), and both (n = 18) risk factors were 17%, 48%, and 78%, respectively. Five-year disease-specific survival rates in patients with none, 1, and both preoperative risk factors were 95%, 69%, and 31%, respectively. Conclusion Carbohydrate antigen 19-9 ≥83 U/mL and tumor size ≥2.2 cm were independent preoperative risk factors for poor outcomes in patients with resectable invasive intraductal papillary mucinous carcinoma.

To date, postoperative prognostic factors for intraductal papillary neoplasm of the bile duct (IPNB) have not been well-established. This study aimed to examine the histopathologic features and postoperative prognosis of the two IPNB subclassifications, as well as factors affecting prognosis, based on the authors’ experience at a single institution. The study enrolled 83 patients who underwent surgical resection for pathologically diagnosed IPNB at the authors’ institution. The clinicopathologic features and postoperative outcomes for these patients were examined. The study also investigated postoperative prognostic factors for IPNB using uni- and multivariate analyses. More than half of the tumors (64%) diagnosed as IPNB were early-stage cancer (UICC Tis or T1). However, none were diagnosed as benign. The multivariate analysis showed that lymph node metastasis (hazard ratio [HR], 5.78; p = 0.002) and bile duct margin status with carcinoma in situ (D-CIS; HR, 5.10; p = 0.002) were independent prognostic factors, whereas MUC6 expression showed only a marginal influence on prediction of prognosis (HR, 0.32; p = 0.07). The tumor recurrence rate and the proportion of locoregional recurrence were significantly greater among the patients with D-CIS than among those with negative bile duct margins, including those patients with low-grade dysplasia. The patients with D-CIS showed a significantly poorer prognosis than those with negative bile duct margins (5-year survival, 38% versus 87%; p = 0.0002). Evaluation of resected IPNBs showed cancer in all cases. Avoiding positive biliary stumps during surgery, including resection of carcinoma in situ, would improve the prognosis for patients with IPNB.

Combined portal vein (PV) resection is performed for pancreatic head cancer to achieve clear resection margins. This can be complicated by the formation of varices due to sinistral portal hypertension after pancreaticoduodenectomy (PD) with combined PV resection. However, clinical strategies to prevent varices formation due to sinistral portal hypertension remain controversial. Moreover, the critical vein among splenic vein (SPV), inferior mesenteric vein, left gastric vein, or middle colonic vein requiring preservation to prevent the development of varices remains unclear.We retrospectively analyzed patients with pancreatic cancer who underwent PD with combined PV resection over 18 years at our institution. Varices were evaluated using enhanced computed tomography (CT) and endoscopy. Preoperative types of porto-mesenterico-splenic confluence, venous drainage, and venous resection types were determined by operative records and CT findings.Of the 108 subjects, the incidence of postoperative varices was observed in 24.1% of cases over 5.6 months. These varices were classified into five types based on location, as pancreaticojejunostomy anastomotic (11.5%), gastrojejunostomy anastomotic (11.5%), esophageal (11.5%), splenic hilar-gastric (23.1%), and right colonic (65.4%) varices. No case of variceal bleeding occurred. Multivariate analysis showed SPV ligation as the greatest risk factor of varices (P 0.001), with a higher incidence of left-sided varices in patients with all the SPV venous drainage sacrificed (60%) than in the others (16.7%). Therefore, sacrificing all the SPV venous drainage was the only independent risk factor of varices (P = 0.049).Preservation of SPV venous drainage should be considered during SPV ligation to prevent post-PD varices.

Objective: We compared the pathological features and stage-matched outcomes of patients with invasive intraductal papillary mucinous carcinoma (IPMC) and invasive ductal carcinoma (IDC) of ...

Background This study aimed to demonstrate the diagnostic ability of 64-row multidetector computed tomography (64-row MDCT) for longitudinal superficial extension of distal cholangiocarcinoma (LSEDC). Methods Twenty-seven patients with distal cholangiocarcinoma (DC) underwent preoperative 64-row MDCT without drainage tubes. LSEDC was diagnosed using curved planar reconstruction images reconstructed from 64-row MDCT, which were compared with pathologic findings. Results LSEDC was observed in 13 patients (48%). Ten patients (37%) had enhancing nonthickened bile ducts extending continuously from the main tumor (type 1). These coincided with pathologic findings of high-grade dysplasia (HGD) in 90.0% of cases; that is, a positive predictive value (9/10). Fourteen patients (52%) had only wall thickening of the main tumor with or without enhancement (type 2). Four patients with HGD in this group were difficult to diagnose. Three patients (11%) had enhancing nonthickened bile ducts not in continuity with the main tumor (type 3). This finding revealed an inflammatory change instead of a carcinoma in the pathologic findings. The sensitivity and specificity of detecting HGD were 75% and 93% on the liver side, 33% and 100% on the duodenal side, respectively. Four patients (67%) with HGD on the liver side were overdiagnosed, and one patient (17%) was underdiagnosed. Most of the patients overdiagnosed on the liver side (3/4 or 75%) had drainage tubes inserted before the MDCT. Conclusions For DC patients without drainage tubes, the 64-row MDCT technique may be useful for diagnosing HGD depicted as LSEDC on the liver side but not as useful on the duodenal side.

Pancreaticoduodenectomy (PD) has recently been improved due to its increased safety. However, postoperative pancreatic fistula (POPF) remains a lethal complication of PD. Identifying novel clinicophysiological risk factors for POPF during the early post-PD period would help improve patient morbidity and mortality. Therefore, this retrospective study aimed to evaluate possible risk factors during the early postoperative period after pancreaticoduodenectomy (PD). Data from 349 patients who underwent PD between 2007 and 2012 were examined retrospectively. All patients were classified into 2 groups: group A, patients without fistulae or biochemical leaks (288 patients), and group B, those with grade B or C POPF (61 patients). Data on various clinicophysiological parameters, including serum and drain laboratory data, were collected. Univariate and multivariate analyses were performed to evaluate POPF predictors. A predictive nomogram was established for these results. Univariate analysis showed that various serum and drain-related factors, such as white blood cell count, C-reactive protein levels, drain amylase (DAMY) levels, and drain lipase (DLIP) levels, were possible POPF risk factors. Multivariate analysis confirmed that postoperative day (POD) 1 DLIP levels (hazard ratio, 15.393; p = 0.037) and decreased rate (POD3/1) of DAMY levels (hazard ratio, 4.415; p = 0.028) were independent risk factors. Further, POD1 DLIP levels and decreased rate of DAMY levels were significantly lower in group A than in group B. The accuracy of nomogram was 0.810. POD1 DLIP levels (> 245 U/mL) and decreased rate of DAMY levels (> 0.44) were POPF risk factors, making them possible biomarkers for POPF.

The efficacy of different types of preoperative biliary drainage for cholangiocarcinoma has been debated over the past two decades. Controversy concerning the use of percutaneous transhepatic biliary drainage (PTBD) versus endoscopic biliary drainage (EBD) still exists. This study aimed to compare the long-term outcomes between PTBD and EBD in patients with distal cholangiocarcinoma. Data of patients diagnosed with distal cholangiocarcinoma who underwent preoperative PTBD or EBD from January 1999 to December 2017 were analyzed retrospectively. Post-surgical outcomes, including the incidence of post-operative complications, peritoneal metastasis, disease-free survival, and overall survival, were analyzed. Survival analyses were also performed after propensity score matching in the PTBD and EBD groups. The incidence of post-operative complications was similar in both groups. The 5-year estimated cumulative incidences for peritoneal metastasis were 14.7% and 7.2% in the PTBD and EBD groups, respectively (p = 0.192). The 5-year disease-free survival rates were 23.7% and 47.3% in the PTBD and EBD groups, respectively (p = 0.015). In the multi-variate analysis for overall survival, PTBD was an independent poor prognostic factor. The 5-year overall survival rates were 35.9% and 56.3% in the PTBD and EBD groups, respectively (hazard ratio 1.85, confidence interval 1.05–3.26, p = 0.035). The results after propensity score matching indicated a poorer prognosis in the PTBD group, with a 5-year survival rate of 35.9% in the PTBD group vs 56.0% in the EBD group (p = 0.044). PTBD should be considered as a negative prognostic factor in distal cholangiocarcinoma patients.

Although adjuvant chemotherapy is considered a standard treatment for resected pancreatic ductal adenocarcinoma (PDAC), its utility in stage ⅠA patients is unclear. We aimed to investigate the recurrence rate, surgical outcome, prognostic factors, effectiveness of adjuvant chemotherapy, and determination of groups in whom adjuvant chemotherapy is effective in patients with stage ⅠA PDAC.We retrospectively analyzed 73 patients who underwent pancreatectomy and were pathologically diagnosed with stage ⅠA PDAC between 2000 and 2018. We evaluated the relation between clinicopathological factors, recurrence rates, and outcomes such as the recurrence-free and disease-specific survival rates (RFS and DSS, respectively).The 5-year RFS and DSS rates were 52% and 58%, respectively. In multivariate analysis, a platelet-to-lymphocyte ratio (PLR) ≥ 170, prognostic nutrition index (PNI) 47.5, and pathological grade 2 or 3 constituted risk factors for a shorter DSS (hazard ratios: 4.7, 4.6, and 4.1, respectively). Patients with 0-1 of these risk factors (low-risk group; n = 47) had significantly higher 5-year DSS rates than those with 2-3 risk factors (high-risk group; n = 26) (80% vs. 23%; P 0.001). Patients in the low-risk group showed similar 5-year RFS rates regardless of whether they received or not adjuvant chemotherapy (75% vs 70%, respectively; P = 0.49). Contrarily, high-risk patients who underwent adjuvant chemotherapy had higher 5-year RFS rates than those who did not receive adjuvant chemotherapy (32% vs 0%; P = 0.045).In stage IA PDAC, adjuvant chemotherapy seems to be effective only in a subgroup of high-risk patients.

The role of pancreatectomy for very elderly patients with pancreatic adenocarcinoma is controversial. This study aimed to clarify the validity of pancreatic resection in octogenarian patients with pancreatic ductal adenocarcinoma. We compared 31 patients aged ≥ 80 years and 548 patients aged < 80 years who underwent pancreatectomy for pancreatic ductal adenocarcinoma and evaluated the relationship between age, clinicopathological factors, recurrence, and outcomes. Postoperative mortality, morbidity, and completion of adjuvant chemotherapy rates did not differ between groups. There were no significant differences in median recurrence–free survival, disease-specific survival, and overall survival between groups (1.0, 2.3, and 2.2 years in patients ≥ 80 years and 1.2, 2.8, and 2.7 years in patients < 80 years; P = 0.67, 0.47, and 0.46, respectively). The median time from recurrence to death of octogenarian patients was significantly shorter than that of younger patients (0.6 vs. 1.1 years, P = 0.0070). In multivariate analysis, age ≥ 80 years (hazard ratio, 1.5), resection of other organs (hazard ratio, 1.8), pathological grade 2/3 (hazard ratio, 1.6), and failure to implement of treatment after recurrence (hazard ratio, 3.6) were independent risk factors for a short time from recurrence to death. Furthermore, age ≥ 80 years (odds ratio, 0.32) was an independent risk factor for the implementation of treatment after recurrence. Pancreatectomy for octogenarians may be acceptable, but median survival time from recurrence to death was shorter due to lower rates of implementation of treatment after recurrence in octogenarian patients.

Although more patients have long-term survival after pancreatectomy, the details of pancreatogenic diabetes mellitus (DM) are still unclear. We aimed to investigate the incidence of new-onset DM (NODM) after distal pancreatectomy (DP) and to clarify the risk factors, including allowable pancreatic resection rate (PR), for NODM.The incidence, onset time, and risk factors for NODM were retrospectively evaluated in 150 patients who underwent DP without preoperative DM and with5 years of postoperative follow-up between 2005 and 2015.The incidence rate of NODM was 39%, and 60% of this incidence was noted within 6 months postoperatively. In the multivariate analysis, hemoglobin A1c ≥ 5.8% (odds ratio [OR] 7.6), impaired glucose tolerance and/or impaired fasting glucose (OR 4.2), homeostasis model assessment of insulin resistance ≥1.4 (OR 5.5), and insulinogenic index0.7 (OR 3.9) were the preoperative risk factors for NODM. Based on these four preoperative risk factors of NODM, we made the new scoring system to predict the NODM after DP. The NODM incidence was 0%, 8%, 48%, 60%, and 86% in patients with risk scores 0 (n = 25), 1 (n = 36), 2 (n = 33), 3 (n = 35), and 4 (n = 21), respectively. PRs ≥42.1% and ≥30.9% were allowable in the preoperative risk-score 0-1 and 2-4 groups. In the former group, the NODM incidence for PR ≥ 42.1% and42.1% was significantly different (20% vs 0%, P 0.05). In the latter group, the NODM incidence for PR ≥ 30.9% vs30.9% was significantly different (75% vs 23%, P 0.05).We clarified the preoperative risk factors and allowable PR for NODM and recommended the use of a risk scoring system for predicting NODM preoperatively.

Background High-risk stigmata (HRS) and ‘worrisome features’ (WFs) are defined as predictive factors for malignancies of intraductal papillary mucinous neoplasms (IPMNs). We performed this study to determine the importance and odds ratio (OR) of each HRS and WFs as predictors for high-grade dysplasia (HGD). Methods We analyzed 295 patients who underwent pancreatectomy for branch duct and mixed-type IPMN, and evaluated the association between HRS and WFs (as defined by the ‘2017 Fukuoka Consensus Guidelines’) and HGD. Results The proportions of patients with low-grade dysplasia (LGD), HGD, and invasive carcinoma were 47%, 28%, and 25%, respectively. Multivariate analysis comparing patients with LGD and HGD using all HRS and WFs revealed that an enhancing mural nodule ≥5 mm (OR: 4.1), pancreatitis (OR: 2.2), and thickened/enhancing cyst walls (OR: 2.2) were independent predictive factors for HGD. Based on the OR (the former factor is two points and the latter two factors are each one point), the incidence of HGD in patients with none (n = 43), one (n = 82), two (n = 25), three (n = 52), and four (n = 19) of these predictive factors were 9%, 26%, 52%, 62%, and 63%, respectively. Assuming a score of one or higher as a surgical indication, the sensitivity, specificity, positive predict value, and negative predict value of HGD were 95, 38, 44, and 91%. Conclusions Our derived scoring system using more important factors in HRS and WFs may be useful for predicting HGD and determining surgical indications of IPMN.

Several studies comparing internal and external stents have been conducted with the aim of reducing pancreatic fistula after PD. There is still no consensus, however, on the appropriate use of pancreatic stents for prevention of pancreatic fistula. This multicenter large cohort study aims to evaluate whether internal or external pancreatic stents are more effective in reduction of clinically relevant pancreatic fistula after pancreaticoduodenectomy (PD).We reviewed 3149 patients (internal stent n = 1,311, external stent n = 1838) who underwent PD at 20 institutions in Japan and Korea between 2007 and 2013. Propensity score matched analysis was used to minimize bias from nonrandomized treatment assignment. The primary endpoint was the incidence of clinically relevant pancreatic fistula. This study was registered on the UMIN Clinical Trials Registry (UMIN000032402).After propensity score matched analysis, clinically relevant pancreatic fistula occurred in more patients in the external stents group (280 patients, 28.7%) than in patients in the internal stents group (126 patients, 12.9%) (OR 2.713 [95% CI, 2.139-3.455]; P 0.001). In subset analysis of a high-risk group with soft pancreas and no dilatation of the pancreatic duct, clinically relevant pancreatic fistula occurred in 90 patients (18.8%) in internal stents group and 183 patients (35.4%) in external stents group. External stents were significantly associated with increased risk for clinically relevant pancreatic fistula (OR 2.366 [95% CI, 1.753-3.209]; P 0.001).Propensity score matched analysis showed that, regarding clinically relevant pancreatic fistula after PD, internal stents are safer than external stents for pancreaticojejunostomy.

Objective: This study aimed to demonstrate the clinical features and postoperative outcomes of extrahepatic bile duct (EHBD) neuroendocrine carcinoma (NEC) and compared with those of adenocarcinoma. Methods: We retrospectively analyzed patients with EHBD cancer operated in our institution between 1995 and 2015. Results: Of 475 patients, 468 had adenocarcinoma, while 7 had NEC/mixed adenoneuroendocrine carcinoma (MANEC) in this study. There were no notable preoperative and pathological features in patients with NEC/MANEC. However, patients with NEC/MANEC had a higher recurrence rate (51.8 vs. 100%, p = 0.016), poorer relapse-free survival (RFS) time (the median RFS time: 35 vs. 12 months, p = 0.006), and poorer overall survival (OS) time (the median OS time: 60 vs. 19 months, p = 0.078) than those with adenocarcinoma. Furthermore, patients with NEC/MANEC had higher rates of liver metastasis (11.9 vs. 85.7%, p < 0.001) than those with adenocarcinoma. In multivariable regression analysis, pathological type with NEC/MANEC was a risk factor for poorer RFS (p = 0.022, hazard ratio: 6.09). Conclusions: Patients with NEC/MANEC have high malignant potential and poor outcomes. It is necessary to develop an effective approach and postoperative adjuvant treatment for patients with NEC/MANEC.

OBJECTIVES This study aimed to identify the detailed clinicopathological features of undifferentiated carcinoma of the pancreas (UCP). METHODS We investigated clinical, imaging features and the prognoses of 261 patients; 8 were our patients, and the remainder were identified by searching English-language articles in PubMed. RESULTS We classified patients with UCP into 3 types based on pathological findings: osteoclast-like giant cell-associated carcinoma, pleomorphic cell carcinoma (PLC), and spindle cell carcinoma. There were no remarkable differences in clinical, radiological features between these 3 types. However, PLCs were significantly more likely to be unresectable than were the other 2 types (P < 0.001). Patients with osteoclast-like giant cell-associated carcinoma achieved the best overall survival (OS) rates (P < 0.001), whereas those with spindle cell carcinoma had significantly longer OS rates than did those with PLC (P = 0.004). These OS patterns were maintained when considering only those patients who underwent resection. Patients with PLC had both lower curative resection and high lymph node metastasis rates (P = 0.029, P = 0.023). Patients who underwent resection had more favorable prognoses than did those who did not. CONCLUSIONS Surgery is the first choice for resectable UCP. Pleomorphic cell carcinoma is particularly malignant; postoperative treatment should be introduced immediately.

To investigate short- and long-term surgical outcomes for patients with perihilar cholangiocarcinoma and vascular invasion. Data from 249 patients who underwent perihilar cholangiocarcinoma surgery between 2000 and 2016 were retrospectively analyzed. Patient evaluations included short-term surgical outcomes following vascular resection and long-term outcomes in cases with histopathological vascular invasion. Mortality was 3.6% overall; 16% for hepatic artery resections, 5.4% for portal vein resections, and 1.7% in the absence of vascular resection (p = 0.029). No between-group differences were observed in the incidence of Clavien–Dindo grade ≥ 3 complications. The factors related to perioperative mortality were hepatic artery resection (odds ratio [OR] = 25.5), right trisectionectomy (OR = 13.0), and central bisectionectomy (OR = 13.8). Multivariate analysis for overall survival identified several prognostic factors: carcinoembryonic antigen level ≥ 5 ng/mL (hazard ratio [HR] = 1.68), poor differentiation (HR = 2.39), distant metastasis (HR = 1.97), and R1 invasive resection (HR = 2.13). Five-year overall survival for patients with portal vein invasion and M0R0/1cis was 35.6%, significantly worse than the 53.4% for patients with no portal vein invasion and M0R/1cis but better than the 0% for patients with portal vein invasion and M1 or R1. Those with hepatic arterial invasion and M0R0/1cis were 24.7%, significantly worse than the 53.4% for patients with no hepatic arterial invasion and M0R0/1cis but significantly better than the 0% for patients with hepatic arterial invasion and M1 or R1. Short-term outcomes for patients with perihilar cholangiocarcinoma and undergoing vascular resection were poor compared to those without vascular resection. Long-term survival in R0M0 disease was more favorable; aggressive surgery is recommended.

Background/purpose We investigated whether the daily level of total bilirubin in the bile (LTB) excreted from the future remnant liver (FRL) can predict post-hepatectomy liver failure (PHLF) in patients with obstructive jaundice undergoing hepatectomy. Methods Seventy-four patients who underwent biliary drainage and collection of bile juice from the FRL before undergoing right hepatectomy or right/left trisectionectomy with bile duct resection were included. The LTB from the FRL (mg/day) was calculated as the volume of the bile (dL) per day multiplied by the density of total bilirubin in the bile (mg/dL). We compared patients' characteristics with or without PHLF, which was defined as the total serum bilirubin level remaining >10 mg/dL after postoperative day 10. Then, pre- and intraoperative factors related to PHLF were examined. Results PHLF was observed in six patients. LTB was significantly lower in the PHLF group. The LTB cut-off value for predicting PHLF, as determined using the receiver operating characteristic curve, was 56 mg/day. On multivariate analysis, LTB was found to be an independent risk factor for PHLF (p=0.01, OR 35.88). Conclusions LTB may be a potential functional assessment in jaundiced patients before right hepatectomy and right/left trisectionectomy.

Little is known regarding the risk of tumor dissemination when percutaneous biliary drainage is used before surgical resection of perihilar cholangiocarcinoma (PHC). We aimed to compare the incidence of tumor dissemination after preoperative endoscopic nasobiliary drainage (ENBD) with that after percutaneous transhepatic biliary drainage (PTBD) for PHC. Data from 208 consecutive patients who underwent PHC resection between 2000 and 2013 were retrospectively analyzed. The influence of drainage type on incidence of tumor dissemination was examined. Seventy-six patients underwent ENBD (37%), 87 underwent PTBD (42%), and 45 underwent surgery without preoperative biliary drainage (WD, 22%). The respective 2- and 5-year estimated cumulative incidences of tumor dissemination in the ENBD group (11.8/14.6%) were lower than in the PTBD group (28.8/35.9%, p = 0.003) and equivalent to that in the WD group (11.2/15.9%, p = NS). PTBD (hazard ratio [HR] vs. ENBD, 2.80) was an independent risk factor for postoperative tumor dissemination in the multivariate analysis. The 2- and 5-year disease-specific survival rates were higher in the ENBD group (67.6/47.3%) than in the PTBD group (56.6/27.8%, p = 0.032) and equivalent to that in the WD group (64.9/53.8%, p = NS). However, drainage type was not an independent risk factor in multivariate analysis of disease-specific survival. For patients with PHC, the associated risk of postoperative tumor dissemination in the ENBD group was lower than in the PTBD group and equivalent to that in the WD group. Thus, ENBD is the ideal procedure for preoperative biliary drainage.

Highlights • Mixed adeno-neuroendocrine carcinoma arising primarily in the bile duct is very rare neoplasm. • The patient with mixed adeno-neuroendocrine carcinoma in the bile duct indicates a poor prognosis. • On imaging studies, a hypervascular tumor is suspicious of mixed adeno-neuroendocrine carcinoma. • Curative resection is the only way to obtain the long-term prognosis, even if these patients have lymph node metastasis., Introduction Neuroendocrine tumors arising primarily in the bile duct are rare. And among these tumors, mixed adeno-neuroendocrine carcinoma (MANEC) is quite uncommon. We report a patient with MANEC who achieved long-term recurrence-free survival. And our case report includes analysis previous case reports. Presentation of case A 66-year-old man underwent investigation for persistent anorexia and fatigue. Laboratory tests showed that the values of hepatobiliary enzymes were increased. On CT, a 10 mm × 8 mm hypervascular tumor was observed in the distal bile duct and the proximal bile duct was markedly dilated. Endoscopic retrograde cholangiography (ERC) also showed a stenosis with a long diameter of 10 mm. Examination of a biopsy specimen obtained from the narrow site of the bile duct at the time of ERC revealed tubular adenocarcinoma. Therefore, pylorus-preserving pancreaticoduodenectomy was performed under a preoperative diagnosis of distal bile duct carcinoma. Postoperative pathologic examination revealed alveolar structures and a mixture of moderately differentiated adenocarcinoma with synaptophysin-positive and chromogranin-A-positive neuroendocrine carcinoma. Therefore, the final diagnosis was MANEC, pT3, pN1, M0, pStage II B (TNM classification of the UICC). Curative resection was achieved and there has been no recurrence after 30 months. Discussion In the previous reports, only five patients (14.7%) survived for 24 months or longer. Median survival was longer (14 months) in the curative resection group and shorter (6 months) in the non-curative resection group. Conclusion Curative resection is essential to achieve long-term survival in patients with bile duct MANEC, even if these patients have lymph node metastasis.

Purpose To investigate the risk factors for post-pancreatectomy hemorrhage (PPH). Methods The incidence, outcome, and risk factors for PPH were evaluated in 1169 patients who underwent pancreatectomy. Results The incidence and mortality rates of PPH were 3% and 11% in all pancreatectomies, 4% and 11% in pancreatoduodenectomy, 1% and 20% in distal pancreatectomy, and 3% and 0% in total pancreatectomy, respectively. Male sex [odds ratio (OR) 2.32], body mass index (BMI) ≥ 25 kg/m2 (OR 3.70), absence of diabetes mellitus (DM; HbA1c ≤ 6.2%; OR 3.62), and pancreatoduodenectomy (OR 3.06) were risk factors for PPH after all pancreatectomies. The PPH incidence was 0%, 1%, 2%, 6%, and 20% in patients with risk scores of 0 (n = 65), 1 (n = 325), 2 (n = 455), 3 (n = 299), and 4 (n = 25), respectively. The differences between risk-score groups 0–2 (2%) and 3–4 (7%) were significant (P P = 0.28). The incidence of POPF post-pancreatoduodenectomy was 20%. BMI ≥ 25 kg/m2 (OR 3.17), serum albumin Conclusion Our study clarified the preoperative risk factors for PPH and recommends using a risk scoring system that includes “absence of DM” for predicting PPH.

Background We examined the utility of transient hepatic attenuation differences (THADs) detected in the arterial phase of computed tomography for the diagnosis of acute gangrenous cholecystitis (AGC). Methods We examined 83 consecutive patients who underwent cholecystectomy within 72 h of undergoing three-phase dynamic computed tomography scans for acute cholecystitis between 2009 and 2018 (histopathological examination later confirmed 42 with AGC, 41 without). The THAD volume (cm3 ) was calculated by multiplying the total area of the enhancing lesions (traced on axial images) by the thickness of the scan (0.5-cm slices). We evaluated the sensitivity and specificity of the THAD volume and other computed tomography findings of AGC. Results The THAD volume was significantly larger in the AGC group than in the non-gangrenous acute cholecystitis group (P 78 cm3 to be an independent predictor of AGC. Conclusions Acute gangrenous cholecystitis can be diagnosed using THAD volume, resulting in improved treatment and fewer serious complications.

Backgrounds: The optimal lymph node dissection range in patients with non-functioning pancreatic neuroendocrine tumors is not yet clear. In this study, we investigated the site and frequency of lymph node metastasis and the significance of lymph node dissection in patients with non-functioning pancreatic neuroendocrine tumors. Methods: This retrospective study analyzed 74 patients who underwent a curative pancreatectomy for non-functioning pancreatic neuroendocrine tumors between 2000 and 2016. The site and frequency of lymph node metastasis and clinicopathological factors were evaluated. Results: The rate of synchronous lymph node metastasis was 17.6%, with 11.1 and 29.4% for tumors with diameters of 10–19 mm and ≥20 mm, respectively. Lymph node metastasis was not observed for tumors with a diameter Conclusions: This study clarified the site and frequency of lymph node metastasis and the optimal range of lymph node dissection in patients with non-functioning pancreatic neuroendocrine tumors.

Objective: Upfront surgery is the standard treatment for resectable pancreatic ductal adenocarcinomas (R-PDACs); however, these tumors often recur. We investigated the factors governing recurrence and prognosis in patients with R-PDAC. Methods: We analyzed 359 patients who underwent upfront surgery for R-PDAC between 2000 and 2016, and evaluated the relationship between clinicopathological factors and recurrence/outcomes. Results: The rate of recurrence was 74% while the median time to recurrence was 1.2 years. On multivariate analysis, carbohydrate antigen 19-9 (CA19-9) >37 U/mL (hazard ratio [HR]: 2.02), tumor size >2.6 cm (HR: 1.50), pathological grade 3 (HR: 2.58), lymph node metastasis (LNM; HR: 1.65), residual tumor (HR: 1.47) and forgoing adjuvant chemotherapy (HR: 1.31) were risk factors for a shorter recurrence-free survival; the median survival time (MST) was 2.8 years. On multivariate analysis, CA19-9 > 37 U/mL (HR: 1.99), tumor size >2.6 cm (HR: 1.43), pathological grade 3 (HR: 2.93), pathological portal vein invasion (HR: 1.48), LNM (HR: 1.79) and forgoing adjuvant chemotherapy (HR: 1.39) were risk factors for shorter disease-specific survival intervals. When examining outcomes according to preoperatively measurable factors (CA19-9 > 37 U/mL and tumor size >2.6 cm), the median time to recurrence and MSTs of patients with none (n = 83), one (n = 112) and both (n = 164) risk factors were 3.2, 1.8 and 0.8 years; and 7.2, 4.0 and 1.7 years, respectively. Conclusions: CA19-9 > 37 U/mL and tumor size >2.6 cm were preoperative independent risk factors for early recurrence and poor outcomes in patients with R-PDAC. Therefore, preoperative treatment should be considered for such patients.

Highlights • G-CSF producing gallbladder carcinoma is rare and has a poor prognosis. • We report a long term survival of G-CSF producing gallbladder carcinoma. • We suggest multidisciplinary therapy prolong the survival of patients with G-CSF producing gallbladder carcinoma., Introduction It is extremely rare for gallbladder carcinoma to produce granulocyte-colony stimulating factor (G-CSF) and such tumors have a poor prognosis. Presentation of case A 67-year-old man was admitted with continuous fever. Laboratory tests showed a leukocyte count of 27,980/μL, serum C-reactive protein (CRP) of 9.2 mg/dL and serum G-CSF of 225 pg/mL. Imaging revealed an irregular gallbladder mass about 90 mm in diameter with peripheral enhancement that also involved the liver and transverse colon. G-CSF producing gallbladder carcinoma was diagnosed. We performed cholecystectomy, partial resection of segments 4 and 5 of the liver, partial resection of the transverse colon, and gastrostomy. Histopathological examination showed gallbladder carcinoma (pT3, pN0, M0, G2, and pStage IIIA by the UICC classification, version 7). On immunohistochemical staining, tumor cells were positive for G-CSF. The leukocyte count was normalized postoperatively and fever subsided immediately after surgery. Two months later, the leukocyte count rose to 56,820/μL and metastases to the liver and lymph nodes were detected by CT. Chemotherapy (gemcitabine plus cisplatin) was started and the leukocyte count was normalized after the first course. The patient has continued chemotherapy and has survived for 16 months postoperatively. Discussion G-CSF producing gallbladder carcinoma has a poor prognosis and most patients die within 12 months of starting therapy. It is rare for patients with recurrence to survive for 16 months after surgery, as in the present case. Conclusion Multidisciplinary therapy (surgery and chemotherapy) may prolong the survival of patients with G-CSF producing gallbladder carcinoma, especially those with recurrence.

Background This retrospective study aimed to evaluate clinicopathological findings of remnant pancreatic cancers in survivors of invasive ductal adenocarcinomas of the pancreas (PDAC). Methods A group of 23 patients out of 826 who had curative resections for PDAC between 1980 and 2011 was identified and treated for metachronous pancreatic cancer. Results The following tubular adenocarcinomas were found at the first surgery: 3 well differentiated, 17 moderately differentiated, 1 papillary, and 1 poorly differentiated. Treatments for the remnant pancreas consisted of remnant pancreatectomy in 12 patients, chemotherapy in 6, and the best supportive care in 5. The mean time to treatment was 74.2 months. The 12 patients who received remnant resections had 10 PDACs and 2 intraductal papillary mucinous carcinomas. The median survival time was 31.6 months, and 8 patients are still alive. Conclusions Long-term survivors after curative resection for pancreatic cancer should receive follow-up for remnant pancreatic cancer, and aggressive resection should be considered for more favorable prognosis of PDAC.

The treatment approach to node-positive gallbladder cancer has unresolved issues with regard to the management of patients with a positive superior retro-pancreatic (level 13a) node, which is the highest level of spread. The American Joint Committee on Cancer remains unclear on the status of the 13a node.This retrospective study consisted of 165 patients with node-positive gallbladder cancer without distant metastasis. Patients were reclassified according to the American Joint Committee on Cancer eighth edition classification. The survival of patients with positive level 13a node was compared with that of patients with N1 disease (T stage-wise) and those with para-aortic nodal disease. A multivariate analysis was performed for factors affecting survival.The 5-year survival of patients with positive level 13a with 1-3 nodes was similar to those with N1 disease (40.2% and 32.9%, respectively) and was better than those with more distant nodal spread (P.05). In univariate and multivariate analyses, intraoperative blood loss (hazard ratio [HR] 1.58), R1 resection (HR 1.87), and T4 disease (versus T2, HR 3.44) were poor prognosticators. Pancreaticoduodenectomy may be beneficial in T2 patients.A positive superior retro-pancreatic node does not worsen the prognosis in an otherwise N1 disease in T1/T2 gallbladder cancer. It behaves like a regional lymph node and should be treated as such.

Insulinomas with multiple neuroendocrine tumour type 1 (MEN1) sometimes have metachronous or recurrent tumours. However, the treatment for these tumours is controversial, and published reports regarding multimodal therapy for insulinomas are limited. We report a 73-year-old woman with recurrent insulinoma with MEN1 successfully controlled by multimodal therapy. She had several complications, and poor performance status. Her hypoglycaemia did not improve after 6-month octreotide LAR; as such, she underwent enucleation of the pancreatic tumour. Within 7 years after the first operation, she underwent four succeeding surgeries for recurrent tumours. Her medications during follow-up were octreotide-LAR and Everolimus. Insulinoma can be managed through various treatment options. Medical treatment includes octreotide-LAR and Everolimus, while surgical approach includes enucleation and pancreaticoduodenectomy. Some tumours, particularly those that are MEN1, can recur repeatedly. Thus, several treatments are needed to control them. We highlight the importance of multimodal therapy, including repeated surgery, for the control of the disease.

The clinical relevance of a high-grade dysplasia/carcinoma in situ (HD/CIS)-positive bile duct margin in perihilar cholangiocarcinoma (PHC) is unclear. We evaluated the surgical outcomes of PHC patients with HD/CIS.Clinicopathological data of 163 consecutive patients who underwent resection of PHC between 2004 and 2013 were analyzed retrospectively.Postoperative states included curative resection (R0) with free margins in 113 patients, non-curative resection with HD/CIS (R1-HD/CIS) in 22 patients, and non-curative resection with any invasive carcinoma margin in 28 patients. Multivariate analyses in the entire cohort showed that lymph node metastasis (hazard ratio [HR] 1.91), distant metastasis (HR 3.87), and non-curative resection with any invasive carcinoma margin (vs. R0; HR 2.06) were significant independent prognosticators. However, in node-negative and distant metastasis-negative PHC patients, histology (HR 2.97), R1-HD/CIS (vs. R0; HR 2.31), and non-curative resection with any invasive carcinoma margin (vs. R0; HR 5.33) were significant independent prognosticators. The 2- and 5-year disease-specific survival rates in node-negative and distant metastasis-negative PHC patients with R1-HD/CIS margins were lower compared with those in patients with R0 margins (2-year, 76.7% vs. 84.3%; 5-year, 37.5% vs. 69.3%; P = 0.026).R1-HD/CIS should be avoided in patients undergoing surgery for node-negative and distant metastasis-negative PHC.

The patient was a 65-year-old man, who had undergone right nephrectomy for renal cancer in 2002. At that time, histopathological examination revealed clear cell carcinoma (pT3a, pN0, M0, and pStage III). Postoperatively, he received natural interferon alpha (6 million units 3 times a week) from November 2002 to February 2005, and showed no evidence of recurrence. However, he noticed dysphagia in March 2012. Endoscopy revealed a pedunculated polypoid tumor in the mid-esophagus and biopsies were taken showing a clear cell carcinoma. Contrast-enhanced thoracoabdominal CT scanning identified a pedunculated polypoid tumor in the mid-thoracic esophagus and enlargement of a lymph node adjacent to the right main bronchus. With a diagnosis of esophageal and lymph node metastases of renal cancer, the patient underwent esophagectomy with right thoracotomy with reconstruction by a posterior mediastinal stomach tube. Postoperative histopathological examination revealed clear cell carcinoma. Because esophageal metastasis of renal cancer is extremely rare, this case is reported here together with discussions of the relevant literature.

s / Pancreatology 13 (2013) S1–S80 S10 group (1 yr; 85.8%, 3 yrs; 56.7%) and ODP group (1 yr; 79.3%, 3 yrs; 44.5%). (P 1⁄4 0.079) Conclusions: There seems to be increasing evidence that LDP is equivalent to ODP for Pancreatic cancer in terms of oncologic outcome. However, long term oncologic result will be required and further randomized prospective studies should be performed to support the validity of LDP for Pancreatic cancer.